Definition of the Sentinel Lymph Node and Basic Principles of Detection

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The sentinel lymph node (SLN) is defined as the first regional lymph node to receive lymphatic fluid from a malignant tumor. Therefore, this node is a "sentinel" for second metastatic lymph node stations and for labeling regional tumor spread. (For editorials and overviews see: Veronesi et al. 1997; Dixon 1998; della Rovere and Bird 1998.) This node is useful for locoregional tumor staging and for subsequent individual related further surgical strategies. In some ways, this has been a logical development after the more or less successful use of lymph-angiography by many radiologists in the 1970s. This older method has been used to detect cancer metastases or infiltration of lymph nodes, for example in cases of prostate or bladder cancer as well as in Hodgkin or non-Hodgkin lymphomas.

The lymphangiographic signs indicating tumor infiltration were filling defects or distorted architecture within the lymph nodes and interruption of lymphatic vessels. Pathologic lymphangiography findings in regional or distant node groups were utilized to assess lymphatic tumor spread.

Recently, labeling of the SLN or nodes for tumor staging and locoregional surgical clearance has been developed or its development has started. This means that the detection of the first node or nodes of a particular tumor may be involved in the lymphogenic spread of the primary, and if this is so more extensive regional lymphadenectomy can follow. When the SLN is negative on pathohis-tological examination extensive lymphadenectomy can be avoided.

This staging procedure has been developed for the following tumor categories: breast cancer (already used in many clinics, but in others still in development); malignant melanomas (already well developed); lung tumors; gastrointestinal tumors and head and neck tumors (discussion and preliminary approaches in progress). In addition, new approaches for tumors of the pelvis (cervix, penis, bladder, prostate, etc.) are also under discussion, as is node labeling of neuroendocrine tumors.

Lymphatic mapping techniques have several objectives, but no generally accepted and practiced uniform concept is universally available.

So far, three strategies for detection of sentinel nodes have been proposed:

• Labeling of the sentinel node(s) with a dye, such as "patent blue," to identify draining lymph vessels and the position(s) of the first regional lymph node(s), which are then surgically removed and examined by the techniques of histology, immunohistochemistry (IHC) and/or the polymerase chain reaction (PCR) (Min et al. 1998);

• Labeling of the sentinel node(s) by 99mTc-colloid scintigraphy;

• Sophisticated nuclear medicine and radiological methods:

- Increased glucose metabolism using [F-18]FDG-PET (fluor-18-fluorodeoxy-D-glucose positron emission tomography) to localize increased metabolism in regional small (<1 cm) lymph nodes (Adler et al. 1997).

- New development of radioimmunolabeling or peptide labeling with surface or cytoplasmic markers (e.g., extracellular domain of Her2/ Neu oncoprotein (p185) or EGFR; CEA, gas-trin, somatostatin receptors) (Schauer et al. 1990, 1992; Marx et al. 1990; Borg et al. 1991). No systematic investigations on these lines have so far been published, and these markers can only be used when an initial aspiration biopsy has identified the tumor as positive specifically for these.

- Tissue-specific magnetic resonance imaging (MRI) contrast agents for the reticuloen-dothelial system, such as superparamagnetic iron oxide nanoparticles (Sinerem or AMI 227), which are presently being investigated in clinical trials for detection of lymph node metastasis (Weissleder et al. 1990 a, b, 1994) (see also chapter 19).

Such investigations of SLNs can help to detect me-tastatic infiltration while it is still in situ before gamma probe imaging analysis.

With these methods, neoplastic infiltration of the lymph nodes can even be detected in palpatory negative sentinel basins. It seems to be clear from the start that these new techniques must be measured in terms of their false-negative rates.

The main questions connected with the significance of localization of a SLN are:

• Can a SLN be defined so as to have significance for primaries with different localizations?

• How is it possible to label the node preopera-tively without influencing the primary tumor, especially by the opening of veins that can be caused by increased local pressure or necrosis, for example after the injection of contrast media, which can induce hematogenous metastatic spread?

• Is biopsy of sentinel node(s) efficient in detecting occult metastases and does it have the potential for selecting patients who may benefit from sentinel node dissection alone?

• Is investigation of the sentinel node really significant in avoidance, for instance, of extended axilla revision in breast cancer patients (levels I and II) in sentinel node-negative cases?

• What is the best method of SLN detection and investigation?

• What are the consequences of positive or negative results of investigation of the sentinel node?

• Does SLN investigation, with avoidance for instance of axilla revision in negative cases, have to be included in the matters discussed with the patient and listed in the informed consent provided by the patient?

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